(700e) Formulation of Super Paramagnetic Iron Oxide Nanoparticles for Cryoprotecting Agent Solutions

Advances in transplantation techniques contribute significantly to improving the quality of life of patients who are affected by terminal organ failure. Despite advances in organ preservation technologies, most organs are not used because they exceed their preservation time. One technology that could enable biobanking of whole organs is cryopreservation by vitrification, where the organ is cooled and stored at a cryogenic temperature using cryoprotecting agent (CPA) solutions. Although vitrifying small tissues has proven successful, it has been difficult to preserve the structural integrity and functional physiology of bulk multicellular tissues and organs. The main challenge is associated to the current rewarming methods, where whole organs are immersed in a temperature-controlled bath, resulting in thermomechanical stresses caused by temperature gradients. One novel approach to overcoming this challenge is nanowarming using mCPA, CPA solution containing superparamagnetic iron oxide nanoparticles (SPIONs). In response to an applied alternating magnetic field (AMF) the SPIONS release heat into their environment. Using mCPA to perfuse the entire organ it will result in more uniform temperature distribution during rewarming.

Nanowarming is at a very early stage of development. Importantly, mCPA solutions containing nanoparticles that are stable for prolonged periods of time and during vitrification/nanowarming have not been reported. We address these limitations by formulating mCPAs consisting of SPIONs with high energy dissipation rates and that are stable against aggregation in CPA solutions during vitrification and nanowarming. As proof of concept, an mCPA was formulated using VS55 solution as the base CPA and hearts as the organ of interest. Colloidal stability in mCPA solutions is achieved by coating the nanoparticles with dense brushes of poly(ethylene glycol) (PEG) polymer, which confers stability in biological media. Furthermore, preliminary results demonstrate ultra-stable SPIONs in CPA pre- and post-nanowarming while achieving high temperature rise rates of up to 320oC/min at 44.4 kA/m, 276 kHz. The temperature rise is a controllable phenomenon by altering the field amplitude and/or changing the concentration of the nanoparticles in the CPA. The novel biomedical imaging technology called Magnetic Particle Imaging (MPI) was used to unambiguously and quantitatively assess the distribution of SPIONs after heart perfusion using mCPA before vitrification and after removing mCPA after rewarming. Together, these methods yield novel mCPAs suitable for perfusion, vitrification, and nanowarming of whole organs with minimal residual iron in tissues post-rewarming.